1. Field of Invention
The present invention relates to the molecular cloning of a gene encoding a polypeptide which modulates cellular response to type I interferon, such polypeptide being a putative component of the interferon type I receptor system, and expression of the gene in a suitable host. The present invention relates to the polypeptide itself, active analogs thereof and processes for obtaining polypeptides with such properties.
2. Information Disclosure Statement
Human and murine cells can be induced to make three classes of interferon (IFN) designated alpha, beta, and gamma on their basis of their antigenic properties and on the type of cell producing them. These IFN's in turn induce a number of changes in human cells which result in establishment of an antiviral, anti-tumor, and/or anticellular state, and cause a number of alterations in the cell membrane including induction and/or increased expression of major histocompatibility complex (MHC) antigens. Lindhal, P. et al (1973), "Enhancement by interferon of the expression of surface antigens on murine leukemia L 1210 cells," Proc. Natl. Acad. Sci.(USA), 70, pp 2785-2788; and Fellous, M. et al (1982), "Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblast and lymphoblastoid cells," Proc. Natl. Acad. Sci.(USA), 79, pp. 3082-3086. Most, or all, of these changes are triggered by the signal generated by interaction of IFN's and their cell surface receptors.
Direct ligand binding studies and binding site competition studies as well as indirect immunological and somatic cell genetic studies demonstrate that the three classes of IFN's interact with interferon sensitive cells through specific binding to one of two types of high affinity receptors on the cell surface (reviewed in Rubinstein, M. and Orchansky, P. (1985), "The Interferon Receptors, "CRC Critical Reviews in Biochemistry, 2 p. 249). All human IFN-alpha's and human IFN-.beta. (Type I IFN's) bind to a chromosome 21-encoded Type I receptor, while human IFN-gamma (Type II IFN) binds to a chromosome 6-encoded Type II receptor which requires a chromosome 21-encoded gene product in order to confer sensitivity. The IFN receptor required for MHC induction and the IFN receptor which triggers antiviral state (AVS) induction share common antigenic determinants and are encoded on human chromosome 21.
The human type I IFN receptor has been estimated to have a molecular weight of 95-140 kDa, based on experiments in which cell membrane having bound .sup.125 I-IFN are cross-linked and run on SDS-PAGE (Razziudin, A. et al. (1984), Proc. Natl. Acad. Sci.(USA), 81 pp. 5504-5508 and Thompson, M. R. et al. (1985), J,. Biol, Chem., 260, pp. 563-571). There is some evidence that the receptor is a glycoprotein and the lower values may be closer to the size of the polypeptide itself.
No admission is made that any reference cited herein qualifies as pertinent prior art. All publications cited herein are hereby incorporated by reference.